The purpose of this clinical study was to determine the efficacy, tolerability, and impact on quality of life of
domperidone--a specific peripherally acting
dopamine antagonist--in the management of symptoms of
gastroparesis, a common and potentially debilitating condition in patients with
diabetes mellitus. In the first phase of this multicenter, two-phase withdrawal study, 287 diabetic patients with symptoms of
gastroparesis of at least 6 months' duration received
domperidone 20 mg QID in a single-masked fashion for 4 weeks. Efficacy was evaluated using a four-point rating scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) for each of the following symptoms:
nausea, abdominal distention/bloating, early satiety,
vomiting, and
abdominal pain. At the end of the first phase, patients with sufficient improvement in their total symptom score (a score < or = 6 and a decrease in score of > or = 5 units from the baseline [selection] visit) were eligible for the 4-week, randomized, placebo-controlled, double-masked withdrawal phase of the study. The impact of
domperidone on quality of life was determined using the Medical Outcomes Study Short Form-36 (SF-36). Of 269 patients with data from the single-masked phase, 208 (77%) qualified for entry into the double-masked phase based on a statistically significant improvement in total symptom score, from a mean score of 10.32 at baseline (initial visit) to 3.79 after 4 weeks of single-masked
domperidone therapy. During the double-masked phase, patients in the placebo group had significantly greater deterioration in total symptom scores compared with patients in the
domperidone group (mean changes of 1.84 and 0.85, respectively). Similar significant differences in favor of
domperidone were seen in the secondary efficacy variables (i.e., patients' diary scores and global assessments of symptoms). The tolerability profile of
domperidone was similar to that of placebo. Patients who responded to
domperidone experienced significant improvements in quality of life, as indicated by the SF-36 physical and mental component summary scores. During the double-masked phase, patients who were randomized to placebo experienced a significant deterioration in the physical component summary score compared with patients in the
domperidone group. The results of this study suggest that
domperidone 20 mg QID provides significant improvement in the upper gastrointestinal symptoms of diabetic
gastroparesis and is well tolerated in patients with this condition.